Src family kinase involvement in rat preglomerular microvascular contractile and [Ca2+]i responses to ANG II

Qi Che, Pamela K. Carmines

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16 Scopus citations


Experiments were performed to investigate the potential role of Src family kinase(s) in the rat afferent arteriolar contractile response to ANG II. The in vitro blood-perfused juxtamedullary nephron technique was employed to monitor afferent arteriolar lumen diameter responses to 1-100 nM ANG II before and during Src family kinase inhibition (10 μM PP2). PP2 did not alter baseline diameter but attenuated ANG II-induced contractile responses by 33 ± 6%. An inactive analog of PP2 (PP3) had no effect on ANG II-induced afferent arteriolar contraction. The effect of Src kinase inhibition on ANG II-induced intracellular free Ca2+ concentration ([Ca2+]i) responses was probed in fura 2-loaded preglomerular microvascular smooth muscle cells (PVSMCs) obtained from explants and studied after 3-5 days in culture. In untreated PVSMCs, ANG II evoked peak (Δ = 293 ± 66 nM) and plateau (Δ = 23 ± 8 nM) increases in [Ca2+]i. In PVSMCs pretreated with PP2, baseline [Ca2+]i was unaltered, but both the peak (Δ = 140 ± 22 nM) and plateau (Δ = 3 ± 2 nM) phases of the ANG II response were significantly reduced compared with untreated cells. PP3 did not alter [Ca2+]i responses to ANG II. Immunoprecipitation and Western blot analysis confirmed that 100 nM ANG II increased phosphorylation of c-Src (at Y416) in PVSMCs. The phosphorylation response was maximal 1 min after ANG II exposure and was prevented by PP2. We conclude that the preglomerular vasoconstriction evoked by ANG II involves rapid c-Src activation with subsequent effects that contribute to the [Ca2+]i response to the peptide.

Original languageEnglish (US)
Pages (from-to)F658-F664
JournalAmerican Journal of Physiology - Renal Physiology
Issue number4 57-4
StatePublished - Apr 2005


  • Afferent arteriole
  • Tyrosine kinase
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Urology


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